REDUCTION IN HUMAN NEUTROPHIL SUPEROXIDE ANION GENERATION BY N-3 POLYUNSATURATED FATTY-ACIDS - ROLE OF CYCLOOXYGENASE PRODUCTS AND ENDOTHELIUM-DERIVED RELAXING FACTOR

Dietary supplementation with n-3 polyunsaturated acids (PUFAs) results in augmented vasorelaxation and reduction in superoxide anion generat ion. Augmented vasorelaxation may be mediated by enhanced generation o f vasodilator prostaglandins and/or endothelium-derived relaxing facto r (EDRF), now thought to be nitric oxide (NO). To determine the import ance of enhanced vasodilator prostaglandins or EDRF-NO in reduction in superoxide anion generation during n-3 PUFAs intake, human polymorpho nuclear leukocytes (PMNs) were incubated with n-6 PUFA arachidonic aci d (AA), or n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic a cid (DHA) (each 10(-7) M) for 1 hr at 37 degrees C. Parallel sets of P MNs were treated with the cyclooxygenase inhibitors indomethacin (10(- 5) M), or aspirin (10(-5) M), or the EDRF-NO synthase inhibitor L-NMMA (10(-3) M) prior to incubation with PUFAs. Superoxide anion generatio n by PMNs was determined by measuring the superoxide dismutase (SOD) i nhibitable reduction of ferricytochrome C. PMNs incubated with EPA or DHA, but not AA, demonstrated marked reduction in superoxide anion gen eration. This reduction in superoxide anion generation by n-3 PUFAs wa s abolished by treatment of PMNs with indomethacin or aspirin, but not by L-NMMA. These observations suggest that n-3 PUFAs decrease superox ide anion generation primarily by a prostaglandin-dependent pathway.